Genetic Factors Associated with Periodontal Disease.
For periodontal diseases, important environmental risk factors include gram-negative anaerobic microorganisms, cigarette smoking and poor oral hygiene.
The theory that genes influence susceptibility to common diseases such as periodontitis is not new or revolutionary. Given complex etiology and pathogenesis of periodontitis, variations in any number or combination of genes that control the development of the periodontal tissues or the competency of the cellular and humoral immune systems could affect an individual’s risk for disease.
Once the genetic basis for the disease has been established, it is important to determine:
(1) Which alleles have a measurable effect on the phenotype
(2) Whether the prevention, diagnosis, or treatment of the disease can be improved once disease alleles are identified.
Aggressive Periodontal Disease:
The search for periodontitis-susceptibility alleles is complicated because:
Multiple causes may exist for the same disease
Different genetic mechanisms may lead to the same clinical endpoint
Evidence from a variety of sources suggests that the risk for aggressive periodontitis disease may be substantially heritable. The disorders, result from the protein or biochemical defects; the mutant alleles may affect the function of phagocytic immune cells or the structure of epithelial, connective tissue, or the teeth themselves. An example is Papillon-Lefèvre syndrome, a rare autosomal recessive disorder characterized by palmoplanter hyperkeratosis and aggressive periodontitis. The destruction in the PLS patients can be arrested by eliminating A. actinomycetemcomitans which suggests that aggressive periodontitis is not a direct result of a gene mutation, but rather the consequence of a specific bacterial infection in a highly susceptible host.
Inherited disorders such as acatalasia, leukocyte adhesion deficiency, and Chédiak-Higashi syndrome highlight the importance of competent phagocytes in the defense against periodontal infections. The immunological defects associated with these syndromes can be profound, and patients generally have systemic infections in addition to periodontitis. Although the mutant alleles responsible for these syndromes maybe uncommon, other, more common alleles at the same loci may serve as candidate markers for nonsyndromic forms of aggressive periodontal disease.
Patients with inherited deficiencies in leukocyte adhesion molecules are at high risk for aggressive periodontal disease, and prepubertal periodontitis in particular.
Aggressive periodontitis aggregates in families, such clustering suggests but does not prove the disease has genetic basis because family members can share deleterious components of their environment as well. Despite of inconsistent conclusions regarding their mode of inheritance, segregation analysis have consistently supported the role of a major gene in the etiology of the Aggressive Periodontitis disease.
In early genetic epidemiologic studies of periodontitis, investigators often compared the distribution of inherited tissue markers between patients and healthy controls. More recent studies have examined variation at the gene rather than the protein level.
Chronic Periodontitis:
Clinicians have long known that susceptibility to periodontitis differs among racial and ethnic groups. Although these differences may be caused by unrecognized environmental factors, they also may be the result of race-based or ethnic-based difference in genetic make-up. Measures of periodontitis and gingivitis are correlated within families. Studies indicated the correlations in clinical periodontal measurements were greater between mothers and offspring than between fathers and offspring. Sibling correlations in this study were generally low and null hypothesis of no familial correlation could not be rejected.
When doing twin studies, it is suggested that host genes may influence initial bacterial colonization of oral cavity, the effects do not persist into adulthood. In other studies the identification of the IL-1 genotype allele appears to interact with the risk for periodontitis.
Clinical Implications of Genetic Studies:
Genetic test may prove useful for identifying patients who are most likely to develop disease, suffer from recurrent disease, or suffer tooth loss as a result of disease. This will be useful in only a subset of patients or populations. It will detect risks for complex diseases. An example is to be able to assess early or aggressive forms to prevent pathogenic microorganisms from colonizing oral cavity and may be effective in preventing disease in highly susceptible individuals.
Genetic information also may prove to be useful in predicting treatment outcomes. The identification of genetic risk factors for periodontitis in no way mitigates the importance of recognizing and controlling important environmental risk factors, for example smoking.
Future of Genetic Studies in Periodontology:
Periodontitis is clearly multi-factorial and researchers need to design studies that examine the role of important environmental and genetic factors simultaneously. Most importantly, identifying specific genetic risk factors may be academically appealing but is of little use unless it leads to improvements in the preservation or treatment of periodontal disease.
Genetic Factors Associated with Periodontal Disease.
For periodontal diseases, important environmental risk factors include gram-negative anaerobic microorganisms, cigarette smoking and poor oral hygiene.
The theory that genes influence susceptibility to common diseases such as periodontitis is not new or revolutionary. Given complex etiology and pathogenesis of periodontitis, variations in any number or combination of genes that control the development of the periodontal tissues or the competency of the cellular and humoral immune systems could affect an individual’s risk for disease.
Once the genetic basis for the disease has been established, it is important to determine:
(1) Which alleles have a measurable effect on the phenotype
(2) Whether the prevention, diagnosis, or treatment of the disease can be improved once disease alleles are identified.
Aggressive Periodontal Disease:
The search for periodontitis-susceptibility alleles is complicated because:
Evidence from a variety of sources suggests that the risk for aggressive periodontitis disease may be substantially heritable. The disorders, result from the protein or biochemical defects; the mutant alleles may affect the function of phagocytic immune cells or the structure of epithelial, connective tissue, or the teeth themselves. An example is Papillon-Lefèvre syndrome, a rare autosomal recessive disorder characterized by palmoplanter hyperkeratosis and aggressive periodontitis. The destruction in the PLS patients can be arrested by eliminating A. actinomycetemcomitans which suggests that aggressive periodontitis is not a direct result of a gene mutation, but rather the consequence of a specific bacterial infection in a highly susceptible host.
Inherited disorders such as acatalasia, leukocyte adhesion deficiency, and Chédiak-Higashi syndrome highlight the importance of competent phagocytes in the defense against periodontal infections. The immunological defects associated with these syndromes can be profound, and patients generally have systemic infections in addition to periodontitis. Although the mutant alleles responsible for these syndromes maybe uncommon, other, more common alleles at the same loci may serve as candidate markers for nonsyndromic forms of aggressive periodontal disease.
Patients with inherited deficiencies in leukocyte adhesion molecules are at high risk for aggressive periodontal disease, and prepubertal periodontitis in particular.
Aggressive periodontitis aggregates in families, such clustering suggests but does not prove the disease has genetic basis because family members can share deleterious components of their environment as well. Despite of inconsistent conclusions regarding their mode of inheritance, segregation analysis have consistently supported the role of a major gene in the etiology of the Aggressive Periodontitis disease.
In early genetic epidemiologic studies of periodontitis, investigators often compared the distribution of inherited tissue markers between patients and healthy controls. More recent studies have examined variation at the gene rather than the protein level.
Chronic Periodontitis:
Clinicians have long known that susceptibility to periodontitis differs among racial and ethnic groups. Although these differences may be caused by unrecognized environmental factors, they also may be the result of race-based or ethnic-based difference in genetic make-up. Measures of periodontitis and gingivitis are correlated within families. Studies indicated the correlations in clinical periodontal measurements were greater between mothers and offspring than between fathers and offspring. Sibling correlations in this study were generally low and null hypothesis of no familial correlation could not be rejected.
When doing twin studies, it is suggested that host genes may influence initial bacterial colonization of oral cavity, the effects do not persist into adulthood. In other studies the identification of the IL-1 genotype allele appears to interact with the risk for periodontitis.
Clinical Implications of Genetic Studies:
Genetic test may prove useful for identifying patients who are most likely to develop disease, suffer from recurrent disease, or suffer tooth loss as a result of disease. This will be useful in only a subset of patients or populations. It will detect risks for complex diseases. An example is to be able to assess early or aggressive forms to prevent pathogenic microorganisms from colonizing oral cavity and may be effective in preventing disease in highly susceptible individuals.
Genetic information also may prove to be useful in predicting treatment outcomes. The identification of genetic risk factors for periodontitis in no way mitigates the importance of recognizing and controlling important environmental risk factors, for example smoking.
Future of Genetic Studies in Periodontology:
Periodontitis is clearly multi-factorial and researchers need to design studies that examine the role of important environmental and genetic factors simultaneously. Most importantly, identifying specific genetic risk factors may be academically appealing but is of little use unless it leads to improvements in the preservation or treatment of periodontal disease.